Treatments for acute bipolar depression are clearly less than ideal. Antidepressants have often shown little benefit for this indication.

Most people with bipolar disorder are maintained on antidepressants, but the evidence base is rather meager. In a recent trial, researchers recruited 70 patients with bipolar disorder, all of whom had responded to a combination of a mood stabilizer and an antidepressant.

We have often heard that bipolar disorder is frequently underdiagnosed, leading to inappropriate treatments. This idea has been confirmed in several studies, but the plot has thickened—research also suggests that bipolar disorder is being overdiagnosed in some settings.

In 2005 and 2006, two trials showed a substantial advantage for quetiapine (Seroquel) over placebo for bipolar depression. Based on these trials, which were known by the acronym BOLDER I and II, quetiapine received an FDA indication for the condition.

The frequency of antidepressant induced mania has been elusive, with some studies finding high rates of manic switching and others finding very few or no manic episodes among patients taking antidepressants.

Researchers (not paid by the drug company) examined data from GlaxoSmithKline’s database of clinical trials for lamotrigine (Lamictal) as a treatment for bipolar depression.

Much of what is confusing and controversial in the treatment of bipolar disorder revolves around the role of antidepressants. Are they dangerous or safe? Are they effective or ineffective? Does it matter whether the patient has Bipolar I or II?

Dr. Zimmerman, you recently published a paper in which you suggested that bipolar disorder is overdiagnosed in some populations. Can you describe that research?

How should we treat patients with both bipolar disorder and a comorbid anxiety disorder? The answer is not straightforward.

The FDA now requires antidepressant drug makers to carry black box warnings about an increased risk of suicidality in children and young adults.